WASHINGTON – Hydroxychloroquine had no short-term efficacy for primary Sjögren’s syndrome in a randomized, double-blind, placebo-controlled trial involving 120 patients.
The favorable overall response rate after 6 months was low and nearly identical at 19.6% and 19.2%, respectively, in 56 patients treated with 400 mg/day of hydroxychloroquine and 64 patients who received placebo, Dr. Jacques-Eric Gottenberg reported at the annual meeting of the American College of Rheumatology.
Favorable overall response was defined as at least a 30% improvement between weeks 0 and 24 in the values on two of three visual analog scales for dryness, pain, and fatigue. Additionally, no significant differences were seen between the groups with respect to evolution of systemic disease activity, dryness, or quality of life, and no significant differences were observed between patients with anti-SSA/SSB autoantibodies; high IgG levels; or systemic, skin, or articular involvement at enrollment, said Dr. Gottenberg of Strasbourg (France) University Hospital.
Among those in the active treatment group, however, a trend toward decreased serum IgG was noted – from 15.5 g/L at enrollment to 13.4 g/L at week 24, compared with 14.2 g/L to 13.0 g/L in the placebo arm. Also, a significant decrease of IgM – from 1.3 g/L to 1.1 g/L vs. no change from 1.4 g/L in the placebo arm – was seen.
Patients included in the study were mostly women (91.7%) with a mean age of 56 years and a median disease duration of 5 years. About 55% had anti-SSA positivity, and nearly a third (30%) had systemic disease involvement at enrollment. The patients’ median EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) scores were 2 and 6.3, respectively.
All patients fulfilled the European-American consensus group criteria for primary Sjögren’s syndrome, and all but one patient in the treatment arm had detectable blood levels of hydroxychloroquine at 6 months, indicating a high level of compliance with the study protocol, Dr. Gottenberg said.
The evolution of systemic disease was measured using the ESSDAI and ESSPRI scores; dryness was measured using Schirmer’s test and unstimulated salivary flow; and quality of life was measured using the short form health survey (SF-36), the Hospital Anxiety and Depression Scale, the Profile of Fatigue and Discomfort scale, and the Sicca Symptoms Inventory.
The findings are important given the frequency at which hydroxychloroquine is prescribed in patients with primary Sjögren’s syndrome. For example, at the time of enrollment in the Assessment of Systemic Signs and Evolution of Primary Sjögren’s Syndrome (ASSESS) prospective cohort, 56% of 395 patients had been or were being treated with hydroxychloroquine, Dr. Gottenberg said, noting that the drug is most often prescribed for arthralgias, synovitis, or purpura but is also prescribed for dryness and fatigue.
Despite the extensive use of hydroxychloroquine in these patients, few studies of its efficacy have been conducted. Except for one small, crossover trial involving only 19 patients, no controlled trials have compared hydroxychloroquine and placebo, he said.
The crossover trial was negative, except for demonstrating beneficial effects on erythrocyte sedimentation rate and IgG and IgM levels.
The current study raises questions about the value of short-term hydroxychloroquine treatment in patients with primary Sjögren’s syndrome, but it does not address the possibility of benefit with long-term treatment. Additionally, analyses are ongoing to determine if treatment has any therapeutic effect in patients with an interferon signature, he said.
Dr. Gottenberg and his colleagues had no disclosures to report.